Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with a short median survival time ranging from 2-5 years, emphasizing the urgent need for effective treatments. Nintedanib and pirfenidone are established therapies for IPF, based on their ability to slow decline in lung function as measured by forced vital capacity (FVC). However, their impact on mortality, acute exacerbations, and side effects, directly affecting patient experiences, remains unclear. This systematic review aims to summarize the effects of nintedanib and pirfenidone on mortality, acute exacerbations, and side effects in patients with IPF. Individual trials showed no significant reduction in all-cause mortality associated with nintedanib or pirfenidone compared to placebo. Pooled analyses suggested a potential reduction in all-cause mortality with antifibrotic therapy. Pirfenidone did not significantly improve IPF-specific mortality, and nintedanib did not reduce respiratory-related deaths. With respect to acute exacerbations, pirfenidone trials reported no significant reduction, while nintedanib trials had mixed results. Nintedanib may reduce acute exacerbations, especially at higher doses. Both therapies caused mild to moderate side effects. The adverse effects of pirfenidone were often dose-dependent and included primarily gastrointestinal symptoms and skin problems. Nintedanib primarily led to diarrhea, occasionally requiring discontinuation. Both drugs caused elevated liver enzyme (transaminase) levels in a small minority of patients, manageable without severe complications. In conclusion, while nintedanib and pirfenidone demonstrate a reduction in all-cause mortality and a slowing of FVC decline in IPF patients, their impact on IPF-specific and respiratory-related mortality, as well as on acute exacerbations (particularly for pirfenidone), is more limited. Moreover, the adverse event profiles, including gastrointestinal issues, skin disorders, and liver enzyme elevations, although mild to moderate, further complicate their use. Side effects such as photosensitivity and persistent diarrhea can significantly impair quality of life, potentially overshadowing the benefits of reduced FVC decline. Therefore, individual treatment decisions must be informed by a comprehensive and balanced understanding of benefits and risks of these drugs.